tetracycline and Pleurisy

Intrapleural loculation can increase morbidity in hemothoraces or parapneumonic effusions. Intrapleural fibrin precedes visceral-parietal pleural adhesions. We speculated that single-chain urokinase plasminogen activator alone or bound to its receptor could prevent these adhesions by their relative resistance to local inhibition by plasminogen activator inhibitors. We found that recombinant human single-chain urokinase-bound rabbit pleural mesothelial cells or lung fibroblasts with kinetics similar to that reported for human cells (kD of approximately 5 nM). The receptor-bound fibrinolysin maintained in vitro fibrinolytic activity in the presence of pleural fluids from rabbits with tetracycline-induced pleural injury over 24 hours. In rabbits given intrapleural single-chain urokinase 24 and 48 hours after intrapleural tetracycline (n = 10 animals), adhesions were prevented, whereas the receptor-complexed form (n = 12) attenuated adhesions versus vehicle/tetracycline-treated rabbits (n = 22, p

Topics: Animals; Anti-Bacterial Agents; Biomarkers; Body Fluids; Cell Count; Disease Models, Animal; Epithelium; Female; Fibrin; Fibroblasts; Pleura; Pleural Effusion; Pleurisy; Rabbits; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Tetracycline; Tissue Adhesions; Urokinase-Type Plasminogen Activator

Sclerosants such as tetracycline (TCN) have often been used in the control of malignant pleural effusions. Although the resultant inflammatory response is probably important in the ensuing pleural fibrosis, the signals responsible for the cellular influx into the pleural space following TCN instillation are not well understood. This study, therefore, sought to determine whether the chemokines interleukin-8 (IL-8), growth-related protein (Gro), and monocyte chemotactic protein-1 (MCP-1) were locally elaborated within the first 72 h following intrapleural TCN administration. TCN induced an exudative effusion with high lactate dehydrogenase activity. Although there was no significant change in the pleural fluid total leukocyte content, the median polymorphonuclear neutrophil concentration decreased from 1.067x10(6) to 2.03x10(5) cells x mL(-1) between 24 and 72 h, whereas the median macrophage concentration increased from 1.44x10(5) to 5.98x10(5) cells x mL(-1) over the same period. Furthermore, IL-8, Gro and MCP-1 concentrations decreased between 24 and 72 h. Immunocytochemistry indicated expression of IL-8 by pleural mesothelial cells 24 h, but not 72 h, following TCN administration. The data suggest that local elaboration of interleukin-8 and growth-related protein, in part of mesothelial origin, may influence neutrophil recruitment in tetracycline-induced pleuritis.

Topics: Analysis of Variance; Animals; Chemokine CCL2; Chemokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Interleukin-8; Leukocyte Count; Neutrophils; Nuclear Proteins; Pleural Effusion; Pleurisy; Rabbits; Statistics, Nonparametric; Tetracycline

Topics: Diagnosis, Differential; Female; Hemorrhage; Hemostasis, Surgical; Humans; Middle Aged; Pleural Effusion; Pleurisy; Pleurodesis; Protein Synthesis Inhibitors; Tetracycline; Thoracic Injuries; Thoracic Surgery, Video-Assisted

The ideal agent to produce pleurodesis has not been identified. Tetracycline, the drug used most commonly in the 1980s, is no longer available. Talc either aerosolized or in a slurry is the agent used just most commonly at the present time, but there are concerns about its safety. Another possibility is silver nitrate, which was widely used in the past, but was abandoned on account of side effects. We hypothesized that lower concentrations of silver nitrate than had been used in the past would be effective in creating a pleurodesis in rabbits. The following medications in a total volume of 2 mL were instilled intrapleurally in three groups of ten anesthetized rabbits: 0.25% or 0.50% silver nitrate and 35 mg/kg tetracycline. Twenty-eight days after the injection, the animals were sacrificed and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.50% silver nitrate produced an effective pleurodesis. The mean degree of gross pleurodesis in the rabbits that received 0.50% silver nitrate (3.4 +/- 1.2) did not differ significantly from that of the rabbits that received tetracycline (3.5 +/- 0.7) (scale 0 to 4). The mean degree of microscopic pleural fibrosis in the rabbits that received 0.50% silver nitrate (3.4 +/- 0.7) did not differ significantly from that of the rabbits that received tetracycline (3.9 +/- 0.3). However, 0.25% silver nitrate was ineffective in creating pleural fibrosis, either grossly or microscopically. No rabbits died after the intrapleural injection of the drugs. There were no observed side effects after the injection of silver nitrate. The present study demonstrates that 0.50% silver nitrate instilled into the pleural space is an effective agent for producing pleurodesis in the rabbit; its effect is comparable to tetracycline 35 mg/kg. This agent should be compared with tetracycline derivatives and talc in studies in humans.

Topics: Analysis of Variance; Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fibrosis; Lung; Pleura; Pleurisy; Pleurodesis; Rabbits; Sclerosing Solutions; Silver Nitrate; Statistics, Nonparametric; Tetracycline

The two agents most commonly used for producing a pleurodesis are tetracycline and bleomycin. Tetracycline is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether bleomycin is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg, or bleomycin, 1.5 or 3.0 IU/kg diluted to a total volume of 1 ml with bacteriostatic saline solution. Twenty-eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of bleomycin was ineffective in creating pleural fibrosis, either grossly or microscopically. The mean degree of gross pleurodesis in the six rabbits who received tetracycline was 2.7 +/- 1.5 (scale 0 to 4), while that in the rabbits who received the highest dose of bleomycin was 0.0 +/- 0.0. Based on this study, we recommend that bleomycin not be used as a pleural sclerosant in patients with nonneoplastic pleural disease, eg, those with pneumothorax, congestive heart failure or cirrhosis, and pleural effusion.

Topics: Analysis of Variance; Animals; Bleomycin; Drug Evaluation, Preclinical; Fibrosis; Male; Pleura; Pleurisy; Rabbits; Sclerosing Solutions; Tetracycline; Time Factors

The histopathologic findings were compared from 20 mg/kg intrapleural tetracycline hydrochloride (TCN) and three doses of intrapleural minocycline hydrochloride (5, 10, and 20 mg/kg) (MCN) in New Zealand white rabbits. Both TCN and MCN produced an early neutrophilic predominant pleural effusion that became mononuclear over 48 h. There was no difference in pleural fluid accumulation, number of adhesions, or histologically measured visceral and parietal pleural thickness between TCN and MCN (all p = ns). The TCN, 20 mg/kg, produced more visceral pleural plaque than MCN, 5 mg/kg (p < 0.05). Increasing MCN doses resulted in greater pleural fluid neutrophil accumulation. With higher dose MCN, greater mesothelial cell desquamation and fibroblast proliferation was evident compared to the 5 mg/kg dose. The MCN and TCN produce similar histopathologic condition in the rabbit pleura which suggests that MCN should cause a similar clinical response in humans.

Topics: Analysis of Variance; Animals; Minocycline; Pleura; Pleural Effusion; Pleurisy; Rabbits; Tetracycline; Time Factors; Tissue Adhesions

Models of pleural injury were established with intrapleural tetracycline, intrapleural carrageenan, and empyema in New Zealand White rabbits to evaluate histologically the pleural inflammatory response from 3 to 90 days. Both tetracycline and empyema models produced increases in the pleural connective tissue layers both above and below the fibroelastic membrane associated with angiogenesis and lymphangiogenesis. The influx of fibroblasts from the pleural surface into acellular fibrin strands formed adhesions between the visceral and the parietal pleurae. Injury to the mesothelial cell ranged from a cuboidal transition to total desquamation with the degree of mesothelial injury associated with the amount of fibrin adherence and the propensity toward fibrosis at 90 days. Intervention to promote the resolution of pleural inflammation without fibrosis should be directed toward preservation of the mesothelial surface, removal of pleural fibrin, and inhibition of fibroblast growth and chemotaxis.

Topics: Animals; Carrageenan; Connective Tissue; Empyema; Macrophages; Neovascularization, Pathologic; Pleurisy; Rabbits; Tetracycline; Time Factors; Tissue Adhesions

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Neoplasms; Pleura; Pleural Effusion; Pleurisy; Suction; Tetracycline; Thoracoscopy

The treatment of 15 patients with neoplastic pleurisy and 25 with spontaneous pneumothorax occurring for the second time is described. All were given endopleural tetracycline therapy for symphyseal purposes. In the neoplastic pleurisy cases, the treatment reduced the number of thoracenteses required. In only 1 case did spontaneous pneumothorax recur a short time after treatment.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Central Nervous System Diseases; Female; Humans; Injections; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pleura; Pleurisy; Pneumothorax; Rectal Neoplasms; Skin Neoplasms; Tetracycline

In 1958-74 altogether 64 cases of bacteriologically verified infections of Listeria monocytogenes were diagnosed in Sweden in children, aged more than 27 days, and in adults. Immunosuppression predisposed to the disease. Thus, many patients had co-existing disorders, such as leukemia and alcoholism. Sixteen patients had been treated with corticosteroids, which were combined with cytostatic drugs in nine. Meningoencephalitis was diagnosed in 52 patients and was fatal in 16. The clinical symptoms did not differ from those in purulent meningitis caused by other bacteria. In the cerebrospinal fluid the cellular response was dominated by polymorphonuclear cells in 29 patients and by mononuclear cells in 20. Ten patients had septicemia, which was fatal in four. Clinical symptoms were dominated by chills, high fever and general prostration. One patient had pleurisy and one an abscess of the neck; both recovered. Serotypes 1 and 4b prevailed and were equally common. Many patients developed raised antibody titers in both the O-agglutination test and the complement fixation test. The titers were often not positive until after a month. Moderate granulocytosis was the rule and monocytosis was rarely seen. Ampicillin alone or combined with an aminoglycoside seemed to be the drug of choice in the treatment of listeriosis. An alternative drug was tetracycline. Most deaths occurred within six days of onset of the illness. Early diagnosis and treatment were imperative. Most patients recovered and serious sequelae were rare.

Topics: Abscess; Adrenal Cortex Hormones; Adult; Aged; Ampicillin; Antineoplastic Agents; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Listeria monocytogenes; Listeriosis; Male; Meningitis, Listeria; Middle Aged; Oxacillin; Penicillin G; Pleurisy; Sepsis; Serotyping; Sulfonamides; Sweden; Tetracycline

Topics: Biopsy, Needle; Body Weight; Celiac Disease; Female; Humans; Hypersensitivity, Delayed; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymphopenia; Middle Aged; Penicillins; Pericarditis; Pleurisy; Tetracycline; Whipple Disease

Topics: Adrenal Glands; Animals; Anti-Inflammatory Agents; Carrageenan; Complement System Proteins; Corticosterone; Edema; Inflammation; Male; p-Methoxy-N-methylphenethylamine; Pleurisy; Rats; Tetracycline; Turpentine

Topics: Adult; Aged; Bronchitis; Empyema; Female; Humans; Male; Middle Aged; Pleurisy; Pneumonia; Tetracycline; Urinary Tract Infections

Topics: Amylases; Bronchitis; Humans; Middle Aged; Pleurisy; Tetracycline

Topics: Antitussive Agents; Bronchial Diseases; Bronchitis; Bronchopneumonia; Hemopneumothorax; Humans; Influenza, Human; Lung Diseases; Oxadiazoles; Pleurisy; Pneumonia; Pneumonia, Viral; Respiratory Tract Infections; Tetracycline